PPID diagnosis

Pituitary Pars Intermedia Dysfunction (PPID) remains the most commonly diagnosed endocrinopathy in the horse. Degeneration of the dopaminergic neurons in the hypothalamus causes a loss of the normal tonic inhibition of the pars intermedia.

Diagnosis in advanced cases is often easy based on the presence of clinical signs. However, laboratory diagnosis is important for less advanced cases and to aid in monitoring the response to treatment.

The recommended diagnostic tests for PPID have not changed in the last few years and diagnosis relies mainly on measurement of basal Adrenocorticotropic hormone (ACTH) concentration or the response to the administration of Thyrotropinreleasing hormone (TRH).

Recent research has focused on learning more about the interpretation of these tests under different circumstances. The result of this is that many more ‘grey-areas’ have become apparent and having a clear cut-off value to reach a diagnosis is more difficult. It is likely that over the next few years, we will be able to reach a better understanding of how to most effectively use and interpret these tests.

This document summarises some of the currently available information, which should help in reaching a diagnosis in clinical practice. An excellent resource is the Equine Endocrinology Group website http://sites.tufts.edu/equinee...

Basal plasma ACTH concentration

This is the recommended first line test Sampling protocol:

Collect a single EDTA blood sample at any time of day • Chill within 3 hours

If there will be a delay between sample collection and analysis then centrifuged plasma can be frozen and is then stable for many weeks. Gravity separated plasma should not be frozen as this will lead to a spurious increase in ACTH concentration

Interpreting the result

When using this test in horses with advanced clinical disease the test has both a high sensitivity and specificity. However, when this test is used as a screening test in horses with a lower incidence of disease (for example younger horses with vague clinical signs) then the positive predictive power of the test falls significantly and many false positives occur.

Season (and specifically day-length) has a major impact on ACTH concentration in normal horses. Healthy horses have a significant increase in ACTH concentration in the Autumn. Recently, much higher cut-off values for the diagnosis of PPID in the Autumn months have been proposed than those that have traditionally been used. There is also much less certainty that testing in the Autumn leads to an increased sensitivity of diagnosis rather than a greater rate of false positive test results.

The following table summarises the suggested cut-offs agreed at the recent ACVIM endocrinology special interest group meeting. Results are listed in pg/ml.

Time of Year

Negative

Equivocal

Positive

Mid-November - Mid-July

<30

30 - 50

>50

Mid-July - Mid-November

<50

50 - 100

>100

Thyrotropin releasing hormone stimulation test (TRHST)

This is currently considered the most accurate test for the diagnosis of PPID. The test relies on an excessive pituitary response to the administration of Thyrotropin-releasing hormone (TRH) in horses with PPID when compared to normal horses.

However, the test still has limitations and ongoing research is needed to help us fully understand how to interpret the results. This test is appropriate when the results of a basal ACTH test have been equivocal, or in a case in which PPID is still suspected despite a negative ACTH test result.

Sampling protocol

Collect an EDTA sample for baseline measurement of ACTH

Inject 1mg TRH intravenously

Collect a second EDTA sample exactly 10 minutes later

The plasma should be handled as described in the ACTH section

Availability of TRH

Pharmaceutical grade TRH is not available on the veterinary or human markets in the UK.

We believe this to be legal via the cascade but full VMD guidance can be found at https://www.gov.uk/ guidance/the-cascade-prescribingunauthorised-medicines

If you need any help ordering TRH or would like us to supply a small quantity of the product please contact Kathryn Thornton on 01638 577754.

Interpreting the result

A cut-off of 100pg/ml was initially used to differentiate between healthy horses and those with PPID. Seasonal differences in the response to TRH occur in healthy horses. This has led to the recommendation that this test is best avoided in the Autumn months.

However, recent work has further evaluated this and this in conjunction with a consensus from the ACVIM special interest endocrinology group has led to the following recommendations. Results are listed in pg/ml.

Time of year

Negative

Equivocal

Positive

December - June

<110

110 - 200

>200

July and November

<110

110 - 250

>250

August / September / October

<110

110 - 500

>500

These guidelines are obviously going to lead to a far greater number of equivocal results. When this happens a decision will have to be made on an individual case basis. In horses with equivocal results that have clinical signs highly suggestive of PPID, or active laminitis, it may be prudent to treat the horse with pergolide. In other situations, it will be more appropriate to wait and retest the horse in 2 – 3 months.

Side effects

Side effects are rare but include trembling, lip-smacking and flehmen type behaviour.

Dexamethasone suppression test

This test was previously considered the gold standard for the diagnosis of PPID. However, this test is much less reliable than the other tests previously discussed. The test is also unreliable in the Autumn months and requires the administration of corticosteroids which is often contra-indicated in horses judged to be at high risk for the development of laminitis. Consequently, this test is not currently recommended.

Other tests in horses with PPID

Insulin dysregulation is a common concurrent problem in horses with PPID. It is good practice to evaluate this as a minimum by measurement of basal insulin and glucose concentrations or by performing a dynamic sugar challenge test (link to insulin document). Performing a TRHST after an oral sugar test has been shown to slightly reduce the ACTH response and hence it may be preferable to perform these tests on different days.

Influence of feeding status, time of the day, and season on baseline adrenocorticotropic hormone and the response to thyrotropin releasing hormone-stimulation test in healthy horses. Domest Anim Endocrinol. 2014 Jul;48:77-83.